Regulation of early peritoneal neutrophil migration by macrophage inflammatory protein-2 and mast cells in experimental peritonitis

被引:67
作者
Mercer-Jones, MA
Shrotri, MS
Heinzelmann, M
Peyton, JC
Cheadle, WG [1 ]
机构
[1] Univ Louisville, Sch Med, Dept Surg, Louisville, KY 40292 USA
[2] Vet Affairs Med Ctr, Louisville, KY USA
关键词
C-X-C chemokine; TNF-alpha; histamine; peritoneal leukocytes;
D O I
10.1002/jlb.65.2.249
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Neutrophil (PMN) migration into the peritoneal cavity in response to fecal peritonitis is an important mechanism of host defense against bacterial invasion, We show that the murine C-X-C (PMN-specific) chemokine, macrophage inflammatory protein-2 (MIP-2), on intraperitoneal injection in mice, causes PMN migration into the peritoneum, MIP-2 mRNA and protein were expressed by peritoneal leukocytes after cecal ligation and puncture (CLP) in mice and neutralization of MIP-2 reduced peritoneal PMN migration, A prerequisite for neutrophil-endothelial adhesion and subsequent migration from the circulation is selectin-mediated rolling, Pretreatment of mice with all anti-P-selectin antibody before intraperitoneal injection of MIP-2 significantly reduced peritoneal PMN nligration, However, there are no reports that a C-X-C chemokine can up-regulate endothelial selectins, We postulated that MIP-2, when injected intraperitoneally, interacts with a cell that is known to release factors that up-regulate endothelial selectins, A likely candidate is the mast cell, which contains histamine and tumor necrosis factor alpha (TNF-alpha), and both of these factors induce selectins, Intraperitoneally injected MIP-2 caused an early significant increase in peritoneal TNF-alpha, whereas histamine levels were unaffected. In a subsequent experiment, mast cell-deficient mice and their normal controls were then injected intraperitoneally with MIP-2 or underwent CLP, Significantly fewer PMNs migrated into the peritoneal cavity in the mast cell-deficient mice after MIP-2 injection or CLP, Thus, our findings indicate that mast cells and MIP-2 are necessary for PMN migration into the peritoneum in response to intra-abdominal infection, and that MIP-2 appears to facilitate this through an increase in TNF-alpha release.
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页码:249 / 255
页数:7
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